There is a growing awareness that nuclear compartmentation is an essential component of nuclear metabolism. This proposal is aimed at studying the estrogen receptor as a model to understand how nuclear comparmentation affects transcriptional activity. To achieve this goal, the subnuclear domains targeted by ER under varying hormonal conditions will studied using high resolution microscopy and colocalization studies with other markers of specific subnuclear domains. The regions within the estrogen receptor responsible for interaction with the nuclear matrix will be analyzed by the generation of deletion constructs and chimeric proteins. Finally, the interaction of ER with transcriptional coactivators and regressors will be analyzed in a nucleoskeletal context to determine how subnuclear compartmentation of these factors regulates gene transcription.